The effect of AVE 0991, nebivolol and doxycycline on inflammatory mediators in an apoE-knockout mouse model of atherosclerosis

被引:18
作者
Jawien, Jacek [1 ]
Toton-Zuranska, Justyna [1 ]
Kus, Katarzyna [1 ]
Pawlowska, Malgorzata [1 ]
Olszanecki, Rafal [1 ]
Korbut, Ryszard [1 ]
机构
[1] Jagiellonian Univ, Sch Med, Chair Pharmacol, Krakow, Poland
来源
MEDICAL SCIENCE MONITOR | 2012年 / 18卷 / 10期
关键词
atherosclerosis model; inflammatory markers; nebivolol; AVE; 0991; doxycycline; E-DEFICIENT MICE; 3RD-GENERATION BETA-BLOCKER; SMOOTH-MUSCLE-CELLS; ACCELERATES ATHEROSCLEROSIS; ATTENUATES ATHEROSCLEROSIS; MATRIX METALLOPROTEINASES; ENDOTHELIAL DYSFUNCTION; ESSENTIAL-HYPERTENSION; RECEPTOR MAS; IFN-GAMMA;
D O I
10.12659/MSM.883478
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: The aim of this study was to investigate whether the 3 different substances that can decrease the development of atherosclerosis - nebivolol, AVE 0991 and doxycycline - could at the same time diminish the level of inflammatory indicators interleukin-6 (IL-6), interleukin-12 (IL-12), serum amyloid A (SAA), and monocyte chemotactic protein-1 (MCP-1). Material/Methods: Forty 8-week-old female apoE-knockout mice on the C57BL/6J background were divided into 4 groups and put on chow diet for 4 months. Three experimental groups received the same diet as a control group, mixed with AVE 0991 at a dose 0.58 mu mol per kg of body weight per day, nebivolol at a dose 2.0 mu mol per kg of body weight per day, and doxycycline at a dose 1.5 mg per kg of body weight per day. At the age of 6 months, the mice were sacrificed. Results: All inflammatory indicators (MCP-1, IL-6, IL-12 and SAA) were diminished by AVE 0991. There was also a tendency to lower MCP-1, IL-6, IL-12 and SAA levels by nebivolol and doxycycline; however, it did not reach statistical significance. Conclusions: Of the 3 presented substances, only AVE 0991 was able to diminish the rise of inflammatory markers. Therefore, drug manipulations in the renin-angiotensin-aldosterone axis seem to be the most promising in the future treatment of atherogenesis.
引用
收藏
页码:BR389 / BR393
页数:5
相关论文
共 53 条
[1]   Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice [J].
Aiello, RJ ;
Bourassa, PAK ;
Lindsey, S ;
Weng, WF ;
Natoli, E ;
Rollins, BJ ;
Milos, PM .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (06) :1518-1525
[2]   Nebivolol, but not metoprolol, improves endothelial function of the corpus cavernosum in apolipoprotein E-knockout mice [J].
Baumhaekel, Magnus ;
Schlimmer, Nils ;
Buyukafsar, Kansu ;
Arikan, Onur ;
Boehm, Michael .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 325 (03) :818-823
[3]   Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction [J].
Benter, Ibrahim F. ;
Yousif, Mariam H. M. ;
Cojocel, Constantin ;
Al-Maghrebi, May ;
Diz, Debra I. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 292 (01) :H666-H672
[4]   Nebivolol:: A third-generation β-blocker that augments vascular nitric oxide release endothelial β2-adrenergic receptor-mediated nitric oxide production [J].
Broeders, MAW ;
Doevendans, PA ;
Bekkers, BCAM ;
Bronsaer, R ;
van Gorsel, E ;
Heemskerk, JWM ;
Egbrink, MGAO ;
van Breda, E ;
Reneman, RS ;
van der Zee, R .
CIRCULATION, 2000, 102 (06) :677-684
[5]   Incidence of new cardiovascular events in patients with and without peripheral arterial disease seen in a vascular surgery clinic [J].
Chhabra, Amit ;
Aronow, Wilbert S. ;
Ahn, Chul ;
Duncan, Kurt ;
Patel, Jay D. ;
Papolos, Alexander I. ;
Sateesh, Babu .
MEDICAL SCIENCE MONITOR, 2012, 18 (03) :CR131-CR134
[6]   Angiotensin-(1-7) downregulates the angiotensin II type 1 receptor in vascular smooth muscle cells [J].
Clark, MA ;
Diz, DI ;
Tallant, EA .
HYPERTENSION, 2001, 37 (04) :1141-1146
[7]   Influence of hypertension, obesity and nicotine abuse on quantitative and qualitative changes in acute-phase proteins in patients with essential hypertension [J].
Cymerys, Maciej ;
Bogdanski, Pawel ;
Pupek-Musialik, Danuta ;
Jablecka, Anna ;
Lacki, Jan ;
Korczowska, Izabela ;
Dytfeld, Joanna .
MEDICAL SCIENCE MONITOR, 2012, 18 (05) :CR330-CR336
[8]   Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice [J].
Daugherty, A ;
Manning, MW ;
Cassis, LA .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (11) :1605-1612
[9]   Endothelial β3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation β-blocker nebivolol [J].
Dessy, C ;
Saliez, J ;
Ghisdal, P ;
Daneau, G ;
Lobysheva, II ;
Frérart, F ;
Belge, C ;
Jnaoui, K ;
Noirhomme, P ;
Feron, O ;
Balligand, JL .
CIRCULATION, 2005, 112 (08) :1198-1205
[10]   The atheroprotective effect of 17β-estradiol depends on complex interactions in adaptive immunity [J].
Elhage, R ;
Gourdy, P ;
Jawien, J ;
Brouchet, L ;
Castano, C ;
Fievet, C ;
Hansson, GK ;
Arnal, JF ;
Bayard, F .
AMERICAN JOURNAL OF PATHOLOGY, 2005, 167 (01) :267-274